5 membered heterocyclic compound.pptx

this ppt include introduction synthesis, physical ,chemical properties, and uses of pyrrole furan and thiophene
also include introduction of 5 membered heterocyclic compound and fused heterocyclic compounds

1. BY – VISHAL SINGH SOLANKI CORPORATE INSTITUTE OF PHARMACY, BHOPAL VISIT MY YOUTUBE CHANNEL – PHARMA RISING OR VISHAL SINGH SOLANKI PYRROLE, FURAN & THIOPHENE BY – VISHAL SINGH SOLANKI PHARMA RISING

2. 1. INTRODUCTION 2. 5 MEMBERED HETEROCYCLIC COMPOUNDS 3. PYRROLE 4. FURANE 5. THIOPHENE CONTENT BY – VISHAL SINGH SOLANKI PHARMA RISING

3. Heterocyclic compounds possess a cyclic structure with two or more different kinds of atoms in the ring. This work is devoted to organic heterocyclic compounds in which the ring contains at least one carbon atom; all atoms other than carbon are considered as  heteroatoms . Heterocyclic compounds are cyclic compounds with the ring containing carbon and other element, the component being oxygen, nitrogen and sulfur. The simplest of the five membered heterocyclic compounds are pyrrole , furan and  thiophene , each of which contains single heteroatoms . The five membered ring contains more than one or two heteroatoms also such as azole , pyrrole ,  thiazole ,  thiadiazole , oxadiazole , triazene , etc. INTRODUCTION PHARMA RISING

4. 5 MEMBERED HETEROCYCLIC COMPOUNDS BY – VISHAL SINGH SOLANKI PHARMA RISING

5. Pyrrole is  a heterocyclic aromatic organic compound, a five- membered ring with the formula C 4 H 4 NH . It is a colorless volatile liquid that darkens readily upon exposure to air. Substituted derivatives are also called pyrroles , e.g., N- methylpyrrole , C 4 H 4 NCH 3 . PYRROLE Chemical formula C 4 H 5 N Molar mass 67.091 g·mol −1 Density 0.967 g cm −3 Melting point −23 °C (−9 °F; 250 K) Boiling point 129 to 131 °C (264 to 268 °F; 402 to 404 K) BY – VISHAL SINGH SOLANKI PHARMA RISING

6. 1. FROM FURAN 2. Hantzsch pyrrole synthesis 3. Knorr pyrrole synthesis 4. Paal–Knorr pyrrole synthesis SYNTHESIS OF PYRROLE BY – VISHAL SINGH SOLANKI PHARMA RISING

7. Pyrrole is prepared industrially by treatment of furan with ammonia in the presence of solid acid catalysts, like SiO 2  and Al 2 O 3 Pyrrole can also be formed by catalytic dehydrogenation of pyrrolidine . 1. FROM FURAN BY – VISHAL SINGH SOLANKI PHARMA RISING

8. The Hantzsch pyrrole synthesis is the reaction of β- ketoesters   (1)  with ammonia (or primary amines) and α- haloketones   (2)  to give substituted pyrroles (3) 2. Hantzsch pyrrole synthesis BY – VISHAL SINGH SOLANKI PHARMA RISING

9. The mechanism starts with the amine ( 1 ) attacking the β carbon of the β- ketoesters ( 2 ), and eventually forming an  enamine  ( 3 ). The enamine then attacks the  carbonyl  carbon of the α- haloketone ( 4 ). This is followed by the loss of H 2 O, giving an  imine  ( 5 ). This intermediate undergoes an intramolecular nucleophilic attack, forming a 5-membered ring ( 6 ). Finally, a hydrogen is eliminated and the pi-bonds are rearranged in the ring, yielding the final product ( 7 ). An alternative mechanism has been proposed in which the enamine ( 3 ) attacks the α-carbon of the α- haloketone ( 4 ) as part of a nucleophilic substitution, instead of attacking the carbonyl carbon. MECHANISM BY – VISHAL SINGH SOLANKI PHARMA RISING

10. The Knorr pyrrole synthesis involves the reaction of an α-amino ketone or an α-amino-β- ketoester with an activated methylene compound. The method involves the reaction of an α- aminoketone   (1)  and a compound containing a  methylene group α to (bonded to the next carbon to) a carbonyl group  (2) . 3. Knorr pyrrole synthesis BY – VISHAL SINGH SOLANKI PHARMA RISING

11. In the Paal–Knorr pyrrole synthesis , a 1,4-dicarbonyl compound reacts with ammonia or a primary amine to form a substituted pyrrole . 4. Paal–Knorr pyrrole synthesis protonated carbonyl is attacked by the amine to form the hemiaminal . The amine attacks the other carbonyl to form a 2,5-dihydroxytetrahydropyrrole derivative which undergoes dehydration to give the corresponding substituted pyrrole . The reaction is typically run under protic or Lewis acidic conditions, with a primary amine. Use of ammonium hydroxide or ammonium acetate (as reported by Paal ) gives the N- unsubstituted pyrrole . BY – VISHAL SINGH SOLANKI PHARMA RISING

12. 1. Basic Character: Pyrrole reacts with dilute hydrochloric acid to give a crystalline hydrochloride. CHEMICAL PROPERTIES OF PYRROLE BY – VISHAL SINGH SOLANKI PHARMA RISING

13. Pyrrole is not only a weak base but also a very weak acid. This is shown by its reactions with potassium hydroxide and Grignard reagents. 2. Acidic Character BY – VISHAL SINGH SOLANKI PHARMA RISING

14. Pyrrole undergoes electrophilic substitution reactions at C-2 because three resonance forms can be written for the intermediate obtained from attack at C-2, whereas only two such forms are possible for substitution at C-3. Consequently the C-2 intermediate is more stable and the product with a substituent at C-2 predominates. Substitution at C-3 occurs only when both the 2-positions (that is, α and α') are blocked. 3. Electrophilic Substitution Reactions BY – VISHAL SINGH SOLANKI PHARMA RISING

15. BY – VISHAL SINGH SOLANKI PHARMA RISING

16. Pyrrole is oxidized by chromium trioxide in acetic acid to give the imide of maleic acid. 4. Oxidation BY – VISHAL SINGH SOLANKI PHARMA RISING

17. Mild reduction of pyrrole with zinc and acetic acid yields 3-pyrroline (2,5- dihydropyrrole ). Catalytic reduction completely hydrogenates the ring system and produces pyrrolidine . 5. Reduction BY – VISHAL SINGH SOLANKI PHARMA RISING

18. When treated with sodium methoxide and Methylene iodide, pyrrole undergoes ring expansion forming pyridine. 6. Ring Expansion Reaction BY – VISHAL SINGH SOLANKI PHARMA RISING

19. When treated with hot ethanolic hydroxylamine, pyrrole undergoes ring opening forming the dioxime of succindialdehyde 7. Ring Opening Reaction BY – VISHAL SINGH SOLANKI PHARMA RISING

20. Pyrrole reacts with aqueous potassium carbonate at 100°C to give pyrrole2-carboxylic acid. 7. Kolbe-Schmitt Carboxylation BY – VISHAL SINGH SOLANKI PHARMA RISING

21. Pyrrole reacts with chloroform in the presence of alkali to yield pyrrole-2- aldehyde (2-formylpyrrole) and 3-chloropyridine. 8. Reimer- Tiemann Formylation BY – VISHAL SINGH SOLANKI PHARMA RISING

22. Pyrrole couples with benzenediazonium chloride in a weakly acidic solution to give 2-phenylazopyrrole. 9. Diazo Coupling BY – VISHAL SINGH SOLANKI PHARMA RISING

23. Polypyrrole is of some commercial value.  N - Methylpyrrole is a precursor to  N - methylpyrrolecarboxylic acid, a building-block in pharmaceutical chemistry. Pyrroles are also found in several drugs, including  atorvastatin ,  ketorolac , and  sunitinib . Pyrroles are used as lightfast red, scarlet, and carmine pigments USES OF PYRROLE PHARMA RISING

24. Furan is  a heterocyclic organic compound, consisting of a five- membered aromatic ring with four carbon atoms and one oxygen atom . Chemical compounds containing such rings are also referred to as furans. Furan is a colorless, flammable, highly volatile liquid with a boiling point close to room temperature. It is soluble in common organic solvents, including alcohol, ether, and acetone, and is slightly soluble in water FURAN BY – VISHAL SINGH SOLANKI PHARMA RISING

25. Chemical formula C 4 H 4 O Molar mass 68.075 g·mol −1 Appearance Colorless, volatile liquid Density 0.936 g/ mL Melting point −85.6 °C (−122.1 °F; 187.6 K) Boiling point 31.3 °C (88.3 °F; 304.4 K) CONTI… Its odor is "strong, ethereal; chloroform-like". It is toxic and may be carcinogenic in humans. BY – VISHAL SINGH SOLANKI PHARMA RISING

26. 1. Industrially, furan is manufactured by the palladium-catalyzed decarbonylation of furfural, or by the copper-catalyzed oxidation of 1,3-butadiene In the laboratory, furan can be obtained from furfural by oxidation to 2-furoic acid, followed by  decarboxylation . It can also be prepared directly by thermal decomposition of pentose-containing materials, and cellulosic solids, especially pine wood. Synthesis of Furan BY – VISHAL SINGH SOLANKI PHARMA RISING

27. The  Feist–Benary synthesis  is an organic reaction between α-halogen  ketones  and β- dicarbonyl compounds to produce substituted furan compounds. 2. Feist–Benary synthesis BY – VISHAL SINGH SOLANKI PHARMA RISING

28. The  Paal–Knorr Synthesis  in organic chemistry is a reaction that generates either furans,  pyrroles , or  thiophenes  from 1,4-diketones. The furan synthesis requires an acid catalyst: Mechanism - 3. Paal–Knorr Synthesis PHARMA RISING

29. 1. Basic Character: • Furan is a weak base like pyrrole . It forms unstable salts with mineral acids. These salts may either polymerize to produce a brown resin or undergo hydrolysis to yield succindialdehyde . Chemical reactions of furan: PHARMA RISING

30. Like pyrrole , it undergoes electrophilic substitution at C-2. Substitution at C-3 occurs only when both of the C-2 positions (α and ά) are already blocked. 2. Electrophilic Substitution PHARMA RISING

31. Furan is reduced by hydrogen in the presence of nickel to produce tetrahydrofuran 3. Reduction: PHARMA RISING

32. Furan undergoes the Diels-Alder reaction. An interesting point about this adduct is that it forms phthalic acid when heated in hydrobromic acid. This is the general reaction for furan adduct. 4. Diels-Alder reaction: PHARMA RISING

33. Furan is used primarily as an intermediate in the synthesis and production of other organic compounds. Hydrogenation of furan over a nickel catalyst produces high yields of tetrahydrofuran and is a source of commercial tetrahydrofuran . Furan may also be used as a starting material in the commercial production of thiophene . Furan is used in the formation of lacquers and as a solvent for resins. It is also used in the production of agricultural chemicals (insecticides), stabilizers, and pharmaceuticals. Uses of Furan PHARMA RISING

34. Thiophene  is a heterocyclic compound with the formula C 4 H 4 S. Consisting of a planar five- membered ring, it is aromatic as indicated by its extensive substitution reactions. It is a colorless liquid with a benzene-like odor . In most of its reactions, it resembles benzene. THIOPHENE PHARMA RISING

35. THIOPHENE Chemical formula C 4 H 4 S Molar mass 84.14 g/mol Appearance colorless liquid Density 1.051 g/ mL , liquid Melting point −38 °C (−36 °F; 235 K) Boiling point 84 °C (183 °F; 357 K) PHARMA RISING

36. 1 . By passing a mixture of acetylene and hydrogen sulphide through a tube containing aluminium oxide at 400°C. SYNTHESIS OF THIOPHENE PHARMA RISING

37. The   Paal–Knorr Synthesis  in organic chemistry is a reaction that generates either furans,  pyrroles , or  thiophenes  from 1,4-diketones . in that of  thiophene  for instance the compound  phosphorus pentasulfide MECHANISM Thiophene synthesis is achieved via a mechanism very similar to the furan synthesis. The initial diketone is converted to a  thioketone  with a sulfurizing agent, which then undergoes the same mechanism as the furan synthesis. 2. Paal–Knorr Synthesis PHARMA RISING

38. 3. By the high-temperature (650 C) reaction of sulphur with butane. (Commercial Method of Preparation). 4. From sodium succinate (Laboratory method): In laboratory thiophene is prepared by heating sodium succinate with phosphorous trisulphide . PHARMA RISING

39. Thiophene is 300 times more reactive than benzene. Thiophene does not show any basic properties. It is much more stable to acids than either pyrrole or furan. Thiophene does not undergo the Diels-Alder reaction. Chemical properties of Thiophene PHARMA RISING

40. Thiophene , like furan and pyrrole , undergoes electrophilic substitution reactions primarily at C-2. Substitution at C-3 occurs only when both of the 2-positions (α and ά) are already occupied. (1) Electrophilic Substitutions: PHARMA RISING

41. Thiophene may be hydrogenated by means of sodium amalgam and ethanol to tetrahydrothiophene . (2). Reduction : PHARMA RISING

42. Catalytic reduction of Thiophene with Raney Nickel results in the removal of Sulphur to form n-butane (3) Desulphurisation : PHARMA RISING

43. Thiophenes are important heterocyclic compounds that are widely used as building blocks in many agrochemicals and pharmaceuticals. The benzene ring of a biologically active compound may often be replaced by a thiophene without loss of activity .   This is seen in examples such as the NSAID  lornoxicam , the thiophene analog of  piroxicam , and  sufentanil , the thiophene analog of  fentanyl . Uses PHARMA RISING

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